Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 5478 | 16657;16658;16659 | chr2:178732629;178732628;178732627 | chr2:179597356;179597355;179597354 |
| N2AB | 5161 | 15706;15707;15708 | chr2:178732629;178732628;178732627 | chr2:179597356;179597355;179597354 |
| N2A | 4234 | 12925;12926;12927 | chr2:178732629;178732628;178732627 | chr2:179597356;179597355;179597354 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs1391157831  |
0.16 | 0.992 | N | 0.658 | 0.4 | 0.672509336206 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 2.91E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/L | rs1391157831 |
0.16 | 0.992 | N | 0.658 | 0.4 | 0.672509336206 | gnomAD-4.0.0 | 1.59225E-06 | None | None | None | None | I | None | 0 | 2.2899E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs1302659663 |
-0.032 | 1.0 | D | 0.663 | 0.425 | 0.440394187108 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | I | None | 0 | 5.82E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/S | rs1302659663 |
-0.032 | 1.0 | D | 0.663 | 0.425 | 0.440394187108 | gnomAD-4.0.0 | 2.05318E-06 | None | None | None | None | I | None | 0 | 4.47908E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65711E-05 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.2434 | likely_benign | 0.2763 | benign | -0.288 | Destabilizing | 0.998 | D | 0.63 | neutral | N | 0.483210794 | None | None | I |
| P/C | 0.8484 | likely_pathogenic | 0.8787 | pathogenic | -0.646 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | I |
| P/D | 0.6707 | likely_pathogenic | 0.7337 | pathogenic | None | Stabilizing | 1.0 | D | 0.653 | neutral | None | None | None | None | I |
| P/E | 0.5736 | likely_pathogenic | 0.6359 | pathogenic | -0.116 | Destabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | I |
| P/F | 0.805 | likely_pathogenic | 0.8623 | pathogenic | -0.596 | Destabilizing | 1.0 | D | 0.69 | prob.neutral | None | None | None | None | I |
| P/G | 0.5661 | likely_pathogenic | 0.6252 | pathogenic | -0.38 | Destabilizing | 1.0 | D | 0.68 | prob.neutral | None | None | None | None | I |
| P/H | 0.4922 | ambiguous | 0.5475 | ambiguous | -0.009 | Destabilizing | 1.0 | D | 0.661 | neutral | N | 0.512470772 | None | None | I |
| P/I | 0.6648 | likely_pathogenic | 0.7208 | pathogenic | -0.196 | Destabilizing | 0.958 | D | 0.59 | neutral | None | None | None | None | I |
| P/K | 0.6442 | likely_pathogenic | 0.7038 | pathogenic | -0.25 | Destabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | I |
| P/L | 0.3569 | ambiguous | 0.4114 | ambiguous | -0.196 | Destabilizing | 0.992 | D | 0.658 | neutral | N | 0.492453959 | None | None | I |
| P/M | 0.6702 | likely_pathogenic | 0.7259 | pathogenic | -0.364 | Destabilizing | 1.0 | D | 0.662 | neutral | None | None | None | None | I |
| P/N | 0.5533 | ambiguous | 0.6097 | pathogenic | -0.02 | Destabilizing | 1.0 | D | 0.69 | prob.neutral | None | None | None | None | I |
| P/Q | 0.4195 | ambiguous | 0.4704 | ambiguous | -0.227 | Destabilizing | 1.0 | D | 0.649 | neutral | None | None | None | None | I |
| P/R | 0.4586 | ambiguous | 0.5062 | ambiguous | 0.175 | Stabilizing | 1.0 | D | 0.689 | prob.neutral | N | 0.494264385 | None | None | I |
| P/S | 0.3049 | likely_benign | 0.365 | ambiguous | -0.385 | Destabilizing | 1.0 | D | 0.663 | neutral | D | 0.533750191 | None | None | I |
| P/T | 0.2971 | likely_benign | 0.3395 | benign | -0.4 | Destabilizing | 0.999 | D | 0.64 | neutral | N | 0.480804485 | None | None | I |
| P/V | 0.5096 | ambiguous | 0.5546 | ambiguous | -0.194 | Destabilizing | 0.994 | D | 0.619 | neutral | None | None | None | None | I |
| P/W | 0.9071 | likely_pathogenic | 0.9386 | pathogenic | -0.673 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | I |
| P/Y | 0.7536 | likely_pathogenic | 0.8086 | pathogenic | -0.368 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | I |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.